EVIDENCE FOR HIGH-RISK HAPLOTYPES AND (CGG)N EXPANSION IN FRAGILE-X SYNDROME IN THE HELLENIC POPULATION OF GREECE AND CYPRUS

The expansion of the trinucleotide repeat (CGG)n in successive generat ions through maternal meiosis is the cause of fragile X syndrome, Anal ysis of CA repeat polymorphisms flanking the FMR-1 gene provides evide nce of a limited number of ''founder'' chromosomes and predisposing hi gh-risk haplotypes related to the mutation, To investigate the origin of mutations in the fragile X syndrome in the Hellenic populations of Greece and Cyprus, we studied the alleles and haplotypes at DXS548 and FRAXAC2 loci of 16 independent fragile X and 70 normal control chromo somes,In addition, we studied 191 unrelated normal X chromosomes for t he distribution and frequencies of CGG alleles, At DXS548, 6 alleles w ere found, 2 (194 and 196) of which were represented on fragile X chro mosomes. At FRAXAC2, 6 alleles were found, 4 of which were present on fragile X chromosomes, Sixteen haplotypes were identified, but only 5 were present on fragile X chromosomes. The highest number of CGG repea ts (greater than or equal to 33) were associated with haplotypes 194-1 47, 194-151, 194-153, and 204-155. The data provide evidence for found er chromosomes and high-risk haplotypes in the Hellenic population. (C ) 1996 Wiley-Liss, Inc.